Fatal nitrosamine poisoning

Abstract

A case is reported in which progressive liver symptoms with rise in bilirubin concentration, hemorrhagic diathesis, and signs of portal hypertension developed three years before death in liver coma. The pathologic and neuropathologic findings are described. The case was clarified after dimethylnitrosamine was demonstrated in food intended for the patient and after it was established that small amounts of nitrosamine could have been repeatedly ingested by the patient over a period of years. Comparable cases of human dimethylnitrosamine poisonings published in the literature are presented. The relatively typical morphologic alterations in the liver are described. Problems involved in the histological interpretation of such liver changes as well as the forensic conclusions to be drawn are discussed.

Toxicological Profile for N-Nitrosodi-n-Propylamine

“…Information regarding death of humans following exposure to N-nitrosodi-n-propylamine by any route was not found. Case reports indicate that intentional oral and accidental inhalation exposures to unknown levels of N-nitrosodimethylamine, however, have resulted in deaths in humans (Barnes and Magee 1954, Cooper.and Kimbrough 1980, Freund 1937, Fussgaenger and Ditschuneit 1980, Pedal et al 1982; these deaths apparently were due 18 2. HEALTH EFFECTS to hepatotoxicity.…”

“…Although it is apparent that N-nitrosodi-n-propy1amine produces hepatotoxicity and hemorrhages in the lungs, stomach, kidney and heart at acute lethal doses in animals, there is only limited information regarding the threshold for these effects following acute exposure and documentation of these effects following intermediate or chronic duration exposure is not available. Although human data are not available, human fatalities due to intentional oral and accidental inhalation exposures to unknown levels of N-nitrosodimethylamine have been described in case reports in which hemorrhagic, necrotic and cirrhotic alterations in the liver and diffuse internal bleeding were observed (Barnes and Magee 1954;Cooper and Kimbrough 1980;Freund 1937;Fussgaenger and Ditschuneits 1980;Pedal et al 1982).…”

Elevated mortality from nonalcohol-related chronic liver disease among female rubber workers: Is it associated with exposure to nitrosamines?

“…Initially this woman was diagnosed with unspecific hepatitis. Based on a small series of liver biopsies, the histopathological history of the disease was described from initial minimal findings of the liver to final cirrhosis [Pedal et al, 1982]. To summarize, several human case reports on occupational or criminal poisoning with NDMA were published.…”

“…Fussgaenger and Ditschuneit [1980] calculated that their case had received a total cumulative dose of approximately 20 mg per kg body weight over a period of about 20 months. In addition, Pedal et al [1982] presented estimates based on dose-effect relationships in rabbits which have approximately the same proportion of liver weight to body weight as men. Assuming, then, that 1-10% of a lethal dose of 15 mg per kg body weight may be adequate to induce cirrhosis of the liver, doses as low as 0.15 mg per kg body weight repeatedly administered over several months would suffice.…”

PI3K-Akt/PKB signaling pathway in neutrophils and mononuclear cells exposed to N-nitrosodimethylamine

“…NDMA, a very toxic nitrosamine, possesses carcinogenic, mutagenic, and teratogenic potentials. NDMA toxicity is primarily associated with industrial exposure, mainly via inhalation; acute intoxications (most of criminal nature) have been reported (Pedal et al, 1982). In general, the long-term effects from exposure to NDMA, even at low doses, include organ damage and neoplastic transformation of cells (Belinsky et al, 1990;Souliotis et al, 1998).…”